Objective: To elucidate the mechanism by which ascites fluid accumulation occurs in certain human and murine neoplastic diseases. A second objective is to evaluate the effect of protease inhibitors such as pepstatin on their ability to prevent or reduce ascites fluid accumulation. Approach: Ascites fluids from murine neoplastic models and from patients with ovarian carcinoma and other diseases are studied for their ability to generate chemical mediators such as leukokinins (polypeptides), which this laboratory believes significant in ascites fluid accumulation. In addition, neoplastic cells obtained in the fluid are tested for acid proteases which are believed to catalyze mediator formation. Protease inhibitors such as Pepstatin are tested against these protease in vitro. Inhibitors found to be effective are tested in vivo in murine models. A second aspect is the isolation of the leukokinins and protein from which it is derived as well as isolation of the acid proteases which catalyze leukokinin formation.